April 20, 2009

A study published in JAMA that is in the medical new today deserves the attention of anyone with diabetes who wonders what their chances are of having a heart attack and what factors correlate with that likeliness of heart attack.

The study was run to determine whether expensive screening of people with diabetes who had no symptoms of heart disease was worth doing. It concluded it wasn't.

It's helpful to know this if you are asymptomatic but your doctor is still trying to push you into having expensive tests, which , as cardiologist Dr. Davis points out, have a high false positive rate and often result in unnecessary, expensive, and dangerous medical procedures.

But two other findings that came out of this study should give hope and reassurance to all people with diabetes who strive for good control. Because what the press is not reporting about this study is that it found far fewer heart attacks than expected in this population and that some truly significant risk factors emerged from it that are not the ones you usually hear about.

In brief, what they did was start out with 1,123 people with Type 2 Diabetes who had no symptoms of heart disease. Half were screened with radioactive stress tests half were not. The study lasted for 7 years with a mean follow up per person of 4.8 years. .

How Did The Researchers Define "No Symptoms of CVD"

It's important to note how "no cardiovascular disease" was defined in this study. The researchers explain it meant:

No angina pectoris or chest discomfort evaluated with a positive Rose questionnaire

No stress test or coronary angiography within the prior 3 years

No history of myocardial infarction, heart failure, or coronary revascularization

These Diabetics had Far Fewer Heart Attacks than Expected

In the "Limitations" section of this study the authors write "The cardiac event rates were significantly lower than originally anticipated at the time of the design of the study."

In fact, in this group of 1,123 people with mediocre blood sugar control whose age mostly ranged from 55 to 65 experienced a grand total of 17 heart attacks (1.5%) and 15 (1.3%) cardiac deaths. In addition there were 15 (1.3%) cases of stroke.

By far the largest number of "cardiac events" in this group were "revascularizations" ie angioplasty and bypass operations of which there were 75 6.7%. As we know, doctors rush to perform these operations at any hint of heart attack so their prevalence may overstate the seriousness of heart disease in this population.

Total deaths from any cause were 33 or 2.9% of the group. Considering their age, this is encouraging news.

Predictors of Cardiac Events

The most interesting part of this study, to me, was the table that presents "Factors Associated With Primary Events" a.k.a. heart attack or cardiac death.

This table which you can find HERE breaks out those who did and did not get heart attacks by various factors. They give a very good idea of what factors really correlated with heart attack over a period of five years in middle aged people with diabetes.

Factors You Can't Change

Seventy-two percent of the heart attacks occurred in males who made up 53% of the total study population. There were only 9 heart attacks among the 522 women in the study over 5 years. This is not surprising, as heart attack in this age group is always far higher among men.

A family history of premature heart disease was a very strong factor distinguishing between those who did and did not have heart attacks. Thirty-four percent of those who had heart attacks had the family history while only 19% of those who did not have heart attacks had it.

Age also mattered. Those with heart attacks were on average 2 years older than those who did not and had had diabetes for 3.6 years longer. Though you can't change those factors either, all the other factors associated with incidence of heart attack are things you can change.

A1c

To no one's surprise, the average A1c of those who had heart attacks was higher than those of people who did not. Those who had heart attacks had a mean A1c of 7.5%. Those who did not had a mean A1c of 7.0%. That's a significant difference. One would like to see heart attack risk broken out by A1c quartile but there were too few events--32 total--for this number to be statistically significant.

Triglycerides

Triglicerides were far higher in the group that had heart attacks than in those who did not, an average of 203 vs 169. The way you lower triglycerides is by cutting down on your intake of carbohydrates. Cutting carbs always drops triglyceride levels dramatically. The drug metformin also will lower triglycerides to some extent.

LDL Cholesterol was slightly higher in the group with heart attacks (mean 129 vs 114) and HDL was only slightly lower (47 vs 50), but after figuring in the standard deviations the actual difference between the two groups look less impressive to me.

Neuropathy

The incidence and extent of neuropathy appears to be a very significant marker of heart attack potential. 53% of those with heart attacks had neuropathy compared to 34% of those without, but when we look at the severity of what neuropathy was present we find that there was more than twice as much numbness in the group with heart attack as in those without--28% vs 12%. There was also twice as much pain--22% vs 11%.

Autonomic neuropathy, which affects heart beat and blood pressure control, was indicated by another bellwether statistic, erectile dysfunction, though incidence of this was not, oddly, broken out by gender making it difficult to interpret the finding that 61% of those with heart attacks had it as opposed to 48% of those without.

But more importantly Cardiac Autonomic Dysfunction was a major factor: 53% of those who had the heart attacks had this compared to 21% who did not.

Severity of Other Diabetic Complications

The microalbumen:creatinine ratio, a measure of kidney function, also hinted at upcoming heart attack. Seventy-seven percent of those who did not have heart attacks had a ratio <30 while only 59% of those who did have heart attacks did. Seventeen percent of those who had heart attacks had ratios over 300 while only 4% of those who did not have heart attacks had these extremely high ratios indicative of advanced kidney dysfunction.

When they looked at peripheral vascular disease, 28% of the people with heart attacks had PAD but only 9% of those who didn't get heart attacks had it. The story was not as dramatic for retinopathy. Slightly more people with heart attacks had it than those who did not, but not dramatically so (19% compared to 15%)

Insulin Use

A higher percent of those who had heart attacks were taking insulin (34% vs 23%) however, given the higher A1c in the heart attack group and the much higher incidence of diabetic complications, it is possible that insulin use here is a marker for a history of high blood sugars and the existence of the severe complications described above rather than a cause of the heart attack.

Factors that Did Not Correlate with Heart Attack Occurrence

Lipid Lowering Drugs

Forty-seven percent of those who had heart attacks and 47% of those who did not have heart attacks were on lipid lowering drugs, i.e. statins. These drugs apparently made no difference.

Blood Pressure Drugs and Blood Pressure

The measures for these were surprisingly close in both groups. Fifty nine percent of those with heart attacks were taking BP drugs 57% were taking them in the group that did not. The average BP in those who had heart attacks was 134/78. In those who didn't it was 131/79. However, it is worth noting that these are both levels defined as "normal" in the population at large. If your blood pressure is much higher, there is a lot of evidence it can promote stroke and heart attack.

Suprising Findings

Higher BMI Protective?

Those with higher BMIs had fewer heart attacks than those who had lower BMIs. The average BMI among those with heart attacks was 28.7%. Those who did not have heart attacks had average BMI of 31.2. This is interesting, as it suggests the people who did not have heart attacks were technically obese while those who did were merely overweight. The waists of both groups were the same, given as 41 cm. This appears to be an error as it translates to a waist circumference of 16.1 inches. I assume they meant 41 inches or 104 cm. One is a bit concerned to see an error of this type slip through peer review as it makes you wonder about the other figures. The people who did not have heart attacks had slightly larger hips on average (correctly given in cm) but the actual difference was only 4 cm--not even 2 inches, small enough that it probably doesn't mean much.

Aspirin Use

Slightly more of those who had heart attacks were taking low dose aspirin than those who did not have heart attacks. (50% vs 45%)

The Bottom Line

What I take from these statistics is this: To lower your true risk of having a heart attack lower your blood sugars to the level that prevents neuropathy, which we know means keeping blood sugars under 140 mg/dl (7.7 mmol/L) at all times.

Keep your triglyerides down. This means cutting back on carbohydrates.

Do all this and you can reduce the voluntary factors associated with a likelihood of heart attack in people with diabetes.

There is no need to obsess about losing weight if you are mildly obese as long as your blood sugar is under control

Don't trust statin drugs to make an major difference in your heart attack risk.

None of this is new, but it's nice to see some statistics in a population large enough to be worth consideration.

A few days ago I attended a diabetes seminar for professionals. I was disappointed about what was stressed - statins for high cholesterol and low fat diet for high triglycerides and cholesterol. No mention of the carbohydrate connection.

"The microalbumen:creatinine ratio, a measure of kidney function, " my recent blood work measures serum creatinine and serum albumin. can i use these values to calculate a microalbumen:creatinine ratio? also, i read the 'eGFR' value was most predictive of kidney function. is that true?

I believe the albumen/creatine ratio they refer to is only from the urine test. The values from the serum test are used to calculate the GFR which is also predictive of kidney disease but not as accurate as the urine test. In any event, the kidney function tests were not highly predictive, though it makes sense that if the vasculature in your kidneys was going bad, it would be likely that your other arteries might be too.

Jenny,Do you have any follow-up on the people whose stories you collected who kept their A1c scores in the 5% range? How are they doing? Did many of them "fall off the wagon"? If not, and they attained the <6% scores with diet + exercise, or diet + exercise + metformin, are they included in studies of people with diabetes?

I occasionally hear from some of the people who have reported to me over the years. Many are doing very well. Some have gone through periods of slacking off on control, but typically they get back on it. It is far more normal to oscillate between great control and sloppiness than it is to be perfect all the time.

I have yet to meet anyone, anywhere who has been in any of the large studies of diabetes. Many of these studies are statistical--they analyze patient records (treating the patients anonomously) without the patients being involved. In active studies where various treatments are tried, they seem to always recruit people who are in poor control to start with, but I have no idea where they find them. (Though recently a lot of drug research has been conducted in places like India where there are few (if any) laws to protect study subjects.

But the saddest thing I hear from many of the people who contact me with good news about their health improvement is how few of their doctors show any interest in what they have done to regain control. They drop A1cs from 8 or 9 to the 5% range and doctors basically ignore it, or in some cases warn them that it is dangerous to lower their A1c based on poorly understood studies where drug toxicity was a factor--even when the patients got their results entirely from diet.

My own experience has been similar. I am coming to the conclusion that the doctor recruitment process is skewed towards choosing as candidates for medical school people who have very little curiosity, people who are good at giving teachers back what they want to hear so as to get good grades. This is confirmed by what friends who are professors who teach pre-meds tell me about their students.

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I was diagnosed with diabetes in 1998. Since then I've kept my A1cs in the 5.0-6.0% range using the techniques you'll find explained at The main Blood Sugar 101 Web Site, where you'll also find extensive discussion of the peer-reviewed research that backs up the statements you read here.

I've also published two books on related subjects, Blood Sugar 101: What They Don't Tell You About Diabetes, which was an Amazon Diabetes bestseller for 3 years and Diet 101: The Truth About Low Carb Diets.